OBJECTIVES: Lymph node metastasis is a prominent clinical feature of tongue squamous cell carcinoma (TSCC) and is associated with a higher mortality rate. Carcinoma-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in tumor progression, and are associated with a poor prognosis. The aim of this study was to examine the role of CAFs in promoting the invasion of TSCC through the epithelial-to-mesenchymal transition (EMT). MATERIALS AND METHODS: A series of matched CAF and normal fibroblast (NF) pairs were assessed for cell morphology and for the expression of alpha smooth muscle actin (α-SMA), stromal cell-derived factor-1 (SDF1), fibroblast-activating protein (FAP), vimentin, and cytokeratin (CK) markers. Transwell assays, Western blot analysis, reverse transcription-PCR, and immunofluorescence staining were used to assess the role of CAFs, as compared to that of NFs, in promoting proliferation, migration, invasion, and EMT in TSCC. RESULTS: Both CAF and NF primary cultures expressed vimentin but not CK. CAFs showed significantly higher α-SMA protein levels, SDF1 secretion, and mRNA levels of α-SMA, SDF1, and FAP. We also found that co-culture with CAFs enhanced the proliferation and invasion of SCC9 cells. Moreover, co-culture with CAFs induced upregulation of the EMT markers fibronectin and vimentin, downregulation of E-cadherin, and enhanced invasion in SCC9 cells. CONCLUSION: These results suggest that CAFs induce EMT marker expression and functional changes in TSCCs.
OBJECTIVES: Lymph node metastasis is a prominent clinical feature of tongue squamous cell carcinoma (TSCC) and is associated with a higher mortality rate. Carcinoma-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in tumor progression, and are associated with a poor prognosis. The aim of this study was to examine the role of CAFs in promoting the invasion of TSCC through the epithelial-to-mesenchymal transition (EMT). MATERIALS AND METHODS: A series of matched CAF and normal fibroblast (NF) pairs were assessed for cell morphology and for the expression of alpha smooth muscle actin (α-SMA), stromal cell-derived factor-1 (SDF1), fibroblast-activating protein (FAP), vimentin, and cytokeratin (CK) markers. Transwell assays, Western blot analysis, reverse transcription-PCR, and immunofluorescence staining were used to assess the role of CAFs, as compared to that of NFs, in promoting proliferation, migration, invasion, and EMT in TSCC. RESULTS: Both CAF and NF primary cultures expressed vimentin but not CK. CAFs showed significantly higher α-SMA protein levels, SDF1 secretion, and mRNA levels of α-SMA, SDF1, and FAP. We also found that co-culture with CAFs enhanced the proliferation and invasion of SCC9 cells. Moreover, co-culture with CAFs induced upregulation of the EMT markers fibronectin and vimentin, downregulation of E-cadherin, and enhanced invasion in SCC9 cells. CONCLUSION: These results suggest that CAFs induce EMT marker expression and functional changes in TSCCs.
Authors: Eva Karamitopoulou; Stefan Haemmig; Ulrich Baumgartner; Cornelia Schlup; Martin Wartenberg; Erik Vassella Journal: Mod Pathol Date: 2017-05-26 Impact factor: 7.842
Authors: Muzafar A Macha; Nissar A Wani; Rais A Ganai; Ajaz A Bhat; Abid Hamid; Sheema Hashem; Mohammad Haris; Sham S Chauhan; Mohammad A Zargar; Surinder K Batra Journal: Adv Exp Med Biol Date: 2020 Impact factor: 2.622
Authors: Rahul Bhome; Marc D Bullock; Hajir A Al Saihati; Rebecca W Goh; John N Primrose; A Emre Sayan; Alex H Mirnezami Journal: Front Cell Dev Biol Date: 2015-05-29